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  1. Abstract

    Opportunistic yeast pathogens arose multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistant (MDR) Candida auris. We show that homologs of a known yeast adhesin family in Candida albicans, the Hyr/Iff-like (Hil) family, are enriched in distinct clades of Candida species as a result of multiple, independent expansions. Following gene duplication, the tandem repeat–rich region in these proteins diverged extremely rapidly and generated large variations in length and β-aggregation potential, both of which are known to directly affect adhesion. The conserved N-terminal effector domain was predicted to adopt a β-helical fold followed by an α-crystallin domain, making it structurally similar to a group of unrelated bacterial adhesins. Evolutionary analyses of the effector domain in C. auris revealed relaxed selective constraint combined with signatures of positive selection, suggesting functional diversification after gene duplication. Lastly, we found the Hil family genes to be enriched at chromosomal ends, which likely contributed to their expansion via ectopic recombination and break-induced replication. Combined, these results suggest that the expansion and diversification of adhesin families generate variation in adhesion and virulence within and between species and are a key step toward the emergence of fungal pathogens.

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  2. Protein aggregation, once believed to be a harbinger and/or consequence of stress, age, and pathological conditions, is emerging as a novel concept in cellular regulation. Normal versus pathological aggregation may be distinguished by the capacity of cells to regulate the formation, modification, and dissolution of aggregates. We find that Caenorhabditis elegans aggregates are observed in large cells/blastomeres (oocytes, embryos) and in smaller, further differentiated cells (primordial germ cells), and their analysis using cell biological and genetic tools is straightforward. These observations are consistent with the hypothesis that aggregates are involved in normal development. Using cross-platform analysis in Saccharomyces cerevisiae, C. elegans, and Xenopus laevis, we present studies identifying a novel disaggregase family encoded by animal genomes and expressed embryonically. Our initial analysis of yeast Arb1/Abcf2 in disaggregation and animal ABCF proteins in embryogenesis is consistent with the possibility that members of the ABCF gene family may encode disaggregases needed for aggregate processing during the earliest stages of animal development. 
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